Note:
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“Your mammogram is suspicious for breast cancer.” “Your biopsy was positive for breast cancer.” These are among the most terrifying words a woman can hear from her doctor. Breast cancer elicits so many fears, including those relating to surgery, death, loss of body image and loss of sexuality. Managing these fears can be facilitated by information and knowledge so that each woman can make the best decisions concerning her care. Optimally, these issues are best discussed with the patient’s doctor on an individual basis. What follows is a review of information on breast cancer intended to aid patients and their families in their navigation through the vast ocean of breast cancer

WHO IS AT RISK FOR BREAST CANCER?

Currently, one in every eight women in the United States develops breast cancer. The exact cause of breast cancer is not known and most likely involves many factors, including genetic, environmental, nutritional and hormonal. Breast cancer is more common in higher socioeconomic groups, unmarried women, urban areas and Jewish women.

The most prominent risk factors for breast cancer are age and gender. Men can develop breast cancer, but women are 200 times more likely to develop breast cancer than men. Breast cancer is four hundred times more common in women who are 50 years old as compared to those who are 20 years old. Seventy-five percent of women who develop breast cancer have no risk factors other than age.

A family history of breast cancer will increase the risk of developing breast cancer in a woman by three to five times. Recently, a breast cancer gene (BR CA 1) has been identified. If a woman has this gene present in her chromosomes, there is an 85% chance of developing breast or ovarian cancer, or both in her lifetime. Fifty percent of these cancers will occur before the age of fifty. This gene is felt to be responsible for only two to four percent of all breast cancer cases. Currently, the test for this gene is available only at certain research centers, and though it is highly predictive of some breast cancers, it is still not clear how best to use this information in treating and counseling patients.

Women who started their menstrual periods before age 12, those who delayed menopause until after age 55, and those who had their first pregnancy after age 30 have a mildly increased risk of developing breast cancer (less than two times the normal risk). Pregnancy and breast feeding have a protective effect in preventing breast cancer. Some studies show that hormone replacement therapy and birth control pills cause a small increased risk of breast cancer, but this has not been confirmed in all studies.

When a breast biopsy demonstrates the development of abnormal cells that are not yet cancerous, called atypical hyperplasia, there is a moderately increased risk of developing breast cancer in the future.

Dietary factors such as high-fat diets and alcohol consumption have been implicated as increased risk factors for breast cancer in some studies. More recent studies have disproven high-fat diets as increasing the risk for breast cancer. Cigarette smoking, caffeine intake, and stress do not appear to increase the risk of breast cancer.

HOW IS BREAST CANCER DIAGNOSED?

Currently, mammography and breast examination serve as the foundation in screening for breast cancer. Mammography is an x-ray examination of the breast. It has the ability to detect a cancer in the breast when it is quite small, long before it may be felt by breast examination. Eighty-five to 90% of all breast cancers are detectable by mammography. Approximately 10 to 15 percent of breast cancers are not visible on mammography, but can be felt on physical examination of the breast.

Since a percentage of breast cancers is not seen on mammography, it is extremely important for a woman to have regular breast examinations as well as mammograms in order to most fully ensure she has no evidence of breast cancer. Breast examination can be performed by the woman’s health professional during the routine physical checkup. It should also be performed monthly by the woman herself using the technique of breast self- examination. It is best to do breast self-examination 3 days after the menstrual period has stopped. Any detected change from the usual appearance or feel is reported to the health professional.

An ultrasound is a test that uses sound waves to visualize structures inside the body. It is often used to distinguish between cysts and solid tumors in the breast. Fluid within cysts can be aspirated (withdrawn with a needle and syringe) for analysis in the laboratory.

If an area of the breast is suspicious for a cancer, a biopsy (removal of a piece of tissue to analyze under the microscope) is usually performed to confirm or deny the diagnosis. Eighty percent of biopsies are not cancerous.

HOW IS THE BREAST DESIGNED?

Breast cancer is not just one disease, but rather is a general term used to describe a number of different types of cancers which occur in the breast. Each different type of breast cancer behaves differently and has a different prognosis. Before describing the different cancers and how they are treated, some background information may be helpful.

The breast is an organ of the body designed to produce milk. The breast contains glands called lobules which produce breast milk. There are also tubes or channels called ducts which transport the milk from the glands to the nipple. The majority of breast cancers begins in either the ducts or the lobules and cancer names are based on their site of origin (i.e., ductal carcinoma of the breast or lobular carcinoma of the breast). The lobules and ducts are supported in the breast by surrounding fatty tissue and ligaments.

There are also blood vessels and lymphatics present in the breast. Lymphatics are small thin channels similar to blood vessels. They do not carry blood, but collect and carry tissue fluid. This fluid ultimately re-enters the blood stream. Breast tissue fluid drains through the lymphatics into the axillary lymph nodes, located in the underarm. Lymph nodes are small glands through which lymphatic channels enter. They filter the lymph fluid and can serve as a barrier to the further spread of bacteria or cancer cells that may have entered the lymph fluid. Lymph nodes are not completely effective in filtering out cancer cells and may spread to other parts of the body despite their presence. Once cancer cells have gained access to either the lymph channels or the blood stream, they have the potential to spread to any area of the body. In breast cancer, these areas are typically the bone, the lungs, the liver and the brain.

Breast cancer is also categorized as invasive (infiltrating) or non-invasive (in-situ). Invasiveness, as it relates to cancer, refers to the cancer’s ability to spread to other parts of the body (metastasize). If a cancer is invasive, it has the capability of growing directly into other parts of the body, or traveling in the blood or lymph fluid to these areas. Non-invasive cancers (in situ cancers) are those cancers which are defined by microscopic criteria as lacking the ability to spread to other parts of the body.

WHAT ARE THE TYPES OF BREAST CANCERS?

The majority of breast cancers can be classified into one of the following categories; infiltrating ductal carcinoma, infiltrating lobular carcinoma, ductal carcinoma in situ, lobular carcinoma in situ, inflammatory carcinoma, Paget’s disease, and cystosarcoma phyllodes. There are other tumors of the breast, such as angiosarcoma, squamous cell cancer and lymphoma, but they are quite rare. These categories are based on the microscopic appearance of the breast tissue obtained with a biopsy sample.

* INFILTRATING DUCTAL CARCINOMA
* INFILATRATING LOBULAR CARCINOMA
* DUCTAL CARCINOMA IN SITU (DCIS)
* LOBULAR CARCINOMA IN SITU (LCIS)
* INFLAMMATORY CARCINOMA
* PAGET’S DISEASE
* CYSTOSARCOMA PHYLLODES

INFILTRATING DUCTAL CARCINOMA

Infiltrating Ductal Carcinoma begins in the cells forming the ducts of the breast. It is the most common form of breast cancer, comprising about 65-85% of all cases. On a mammogram, invasive ductal carcinoma is usually found as an irregular mass, or as a group of small white irregular dots called microcalcifications, or a combination of both. It may also appear as a lump in the breast. On physical examination, this lump usually feels much harder or firmer than other benign causes of lumps in the breast.

INFILATRATING LOBULAR CARCINOMA

Infiltrating Lobular Carcinoma comprises 5 to 10 percent of breast cancers. This type of breast cancer can appear similar to infiltrating ductal carcinoma on mammography, but on examination of the breast there is usually not a hard mass, but rather a vague thickening of the breast tissue. Lobular carcinoma can occur in more than one site in the breast (multicentric) or in both breasts simultaneously (bilateral).

DUCTAL CARCINOMA IN SITU (DCIS)

Ductal Carcinoma In Situ (DCIS) is a pre-invasive form of breast cancer. It is commonly seen in association with an invasive breast cancer. If it occurs without an invasive cancer there is usually no lump associated with it. On mammography, there may be fine microcalcifications which can signal its presence. DCIS is frequently multifocal, meaning it is located in more than one area of the breast. Approximately one-third of DCIS cases are multifocal. If DCIS is treated with biopsy alone, about 40% of women will ultimately develop an invasive cancer of that breast in the future.

LOBULAR CARCINOMA IN SITU (LCIS)

Lobular Carcinoma In Situ (LCIS) is usually encountered as an incidental finding in a breast biopsy. It has no symptoms, and has no characteristic pattern on mammography. It has been found to occur in multiple sites in the same breast in 40 to 90% of cases. In 50% of the cases, it may also occur in the opposite breast. The risk of developing an invasive cancer of the breast with LCIS is approximately 1% per year. The invasive cancer that develops has about an equal chance of being in either breast regardless as to which breast the LCIS was initially found. A large percentage (38%) of women with LCIS may not develop an invasive cancer until more than 20 years after the initial diagnosis.

INFLAMMATORY CARCINOMA

Inflammatory carcinoma of the breast is a subtype of infiltrating ductal carcinoma, but is named for its typical clinical presentation. The breast becomes red, swollen, and warm, and the skin becomes quite thickened. The breast appears as if it were infected. This appearance is due to the rapid growth of the cancer which blocks the lymphatics in the breast, causing it to swell and appear infected. The cancer has already spread to the lymph nodes in 90% of the cases at the time of diagnosis. The prognosis for this cancer is very poor, and is fortunately relatively uncommon.

PAGET’S DISEASE

Paget’s disease of the breast accounts for about one to four percent of all breast cancers. It occurs typically as a crusting and scaling of the nipple. It can be mistaken for a benign skin condition unless there is a high index of suspicion.

CYSTOSARCOMA PHYLLODES

Cystosarcoma Phyllodes is a firm tumor that resembles a benign fibroedenoma. This cancer is very different than other cancers of the breast. It seldom spreads to the lymph nodes, but can metastasize to other parts of the body by way of the bloodstream.

WHAT TREATMENTS ARE USED FOR INVASIVE BREAST CANCER?

Currently, when breast cancer is detected it is already an invasive cancer in the majority of cases. The treatment of invasive breast cancer is similar, whether it be invasive ductal or invasive lobular carcinoma.

The treatment plans are divided into local therapy and systemic therapy. Local therapy is designed to remove or kill the cancer cells in the breast and adjacent lymph nodes. If the cancer has not spread outside these areas, the patient can be cured by local therapy alone. Unfortunately, breast cancer can metastasize or spread to other areas of the body even though the primary cancer is quite small and there is no evidence of cancer spread to the lymph nodes. Breast cancer does not always follow a predictable pattern of growth. From many studies, estimates of the risk of metastasis and recurrence of the cancer are given based on factors, such as tumor size, cell type, lymph node status, and hormone receptors. But in any individual woman, an outcome (or prognosis) cannot be predicted with certainty. Due to this uncertainty, a systemic therapy is incorporated to treat the potential and actual risk of cancer cells spreading elsewhere. This systemic therapy is called chemotherapy, and utilizes drugs to kill cancer cells.

Local therapy involves surgery, radiation, or both. There are many terms used in connection with breast cancer surgery. Mastectomy is a general term for removal of the breast. A modified radical mastectomy involves removal of the breast and the axillary lymph nodes. A simple mastectomy removes the breast, but not the lymph nodes. Lumpectomy, partial mastectomy, and quadrentectomy refer to removing only a portion of the breast. An axillary dissection means removal of a portion of the lymph nodes under the arm.

Radiation therapy is the use of special high energy x-ray beams to kill rapidly growing cells, such as cancer cells. It is a generally a painless treatment and is given in an outpatient setting without the need for hospitalization.

A woman who has developed an invasive breast cancer usually has several surgical options for treatment. A modified radical mastectomy or removal of the entire breast, nipple complex and lymph nodes, is one well established option. This is inherently quite a physically deforming operation and less disfiguring treatments for breast cancer now exist. Breast conservation treatment for invasive breast cancer consists of lumpectomy (removal of the breast cancer and a surrounding rim of normal tissue), axillary dissection (removal of a portion of the lymph nodes under the arm), and radiation therapy to the remaining breast tissue. This maintains the majority of a woman’s breast and often the shape is not altered significantly. Many studies have compared these two techniques of therapy and both are equally effective in the treatment of invasive breast cancer. The survival rates at 5 and 10 years for both these therapies are the same. Neither therapy can guarantee a cure of the breast cancer as approximately 25-30% of women will ultimately die from their disease.

The choice of breast conservation therapy or modified radical mastectomy is usually an option available to most women with breast cancer. There are some conditions which pose relatively higher risks with breast conservation therapy. These include multiple sites of invasive breast cancer in the same breast, multiple sites of associated ductal carcinoma in situ, a primary breast cancer that was not detected on mammography, a breast that is difficult to evaluate on physical examination or by mammography, the inability to obtain margins that are clear of cancer at the time of lumpectomy, and cancers that are large in comparison to the breast size, which when removed, would lead to severe breast deformity. These conditions tend to have either a higher risk of local recurrence or make the early detection of a local recurrence in the conserved breast difficult if treated with breast conservation therapy. The risk of local recurrence with breast conservation therapy is about 5-7%. The local recurrence rate following modified radical mastectomy is 1-2%.

If modified radical mastectomy is chosen by a woman as the treatment of her breast cancer, then reconstructive surgery to recreate the breast mound can be done either at the time of mastectomy or at a later time. There are several operations that can be performed to reconstruct the breast. Reconstruction can be done with a woman’s own tissue (autologous reconstruction) or a prosthetic implant can be placed.

A prosthetic implant is usually inserted beneath the pectoralis muscle of the chest. There is usually not enough skin left after a mastectomy to place an adequately sized implant. Therefore, a tissue expander is commonly used. This is a balloon- shaped silicone implant which when initially inserted is flat. The tissue expander can be then filled with fluid externally by means of a small valve under the skin. The implant is filled over a period of several months after the operation. This enlarges the tissue expander and stretches the skin until an appropriately sized permanent implant can be placed which simulates the size of the opposite breast.

In autologous reconstruction, the woman’s own tissue is used to reconstruct the breast. A transverse rectus abdominis myocutaneous flap (TRAM flap) or a latissimus dorsi myocutaneous flap are currently the most used. The TRAM flap uses a portion of the abdominal muscles, fat and skin to reconstruct the breast. The latissimus dorsi myocutaneous flap uses a muscle of the upper back along with its overlying skin to reform the breast.

Nipple reconstruction can also be done in conjunction with any of the reconstructive breast procedures.

WHAT HAPPENS AFTER THE SURGICAL PROCEDURE?

Once the surgical procedure has been completed, whether it has been a breast conservation technique or a modified radical mastectomy, the status of the lymph nodes will be known. The presence or absence of cancer in the lymph nodes plays an important role in determining further treatment. If the cancer has spread to the lymph nodes, the risk of the cancer recurring is much higher and the addition of chemotherapy and/or hormonal therapy is usually indicated.

Chemotherapy and hormonal therapy, used in addition to surgery, is known as adjuvant systemic therapy. The purpose of this therapy is to eradicate microscopic deposits of breast cancer cells which still may be present in other areas of the body. The risk of these metastatic cancer cells roughly increases with the size of the original tumor, whether or not there is spread to the lymph nodes, the number of lymph nodes involved, and the microscopic characteristics of the cancer. There are no tests currently available which can tell doctors precisely whether there is microscopic spread of breast cancer. This is important because even when the cancerous tumor is small and there is no evidence of spread to the lymph nodes, there may be reasons to use adjuvant systemic therapy, since approximately 10%-15% of women in this group will still develop metastatic breast cancer.

Chemotherapy in adjuvant breast cancer treatment usually involves using a combination of drugs, typically, cyclophosphamide (CYTOXAN or NEOSAR), methotrexate, and 5-flourouracil (CMF), or cyclophosphamide, doxorubicin (ADRIAMYCIN, RUBEX) and 5-flourouracil. Currently, six cycles of chemotherapy which encompasses about six months of therapy is standard.

Breast cancer tissue is also tested for estrogen and progesterone receptors, or the so-called hormone receptors. A certain percentage of breast cancers will have molecular sites in their cells to which these hormones will attach. The hormones have a role in promoting the growth of cancerous cells. If these hormone receptors are present, the use of an anti-estrogenic agent called tamoxifen can be used. In older, post-menopausal women it can decrease the risk of recurrent breast cancer similar to the decrease seen with the use of chemotherapy. This avoids many of the side effects of chemotherapy which may include nausea, vomiting, hair loss, loss of energy, susceptibility to infection, and heart toxicity. Tamoxifen, however, can increase the risk of uterine cancer. Tamoxifen can also be given following the completion of chemotherapy because in certain women it can decrease the risk of cancer recurrence even further than with just chemotherapy alone. The optimal duration of treatment with tamoxifen is not known and most regimens range from two to five years. There are ongoing studies to help answer this question.

Inflammatory cancer of the breast is a rapidly growing cancer which has often metastasized at the time of diagnosis. A combination of surgery, radiation therapy and chemotherapy is currently now used. Mastectomy is not performed first as is typically the case in breast cancer. Rather, chemotherapy is started immediately. Radiation therapy to the breast follows and surgery is performed subsequently. This sequencing of treatment has shown to provide the best survival statistics compared to other regimens.

Paget’s disease of the breast is treated similarly to other forms of invasive breast cancer. A modified radical mastectomy is the usual treatment of choice. Lumpectomy which includes removing the nipple complex, followed by radiation therapy is sometimes used.

Cystosarcoma phyllodes cancer of the breast spreads somewhat differently than other breast cancers. It is rare for this cancer to ever spread to the lymph nodes, but it does spread through the blood stream. Since it does not involve the lymph nodes, treatment does not involve removing the lymph nodes, even if the tumor is quite large. Treatment consists of removing the tumor with a rim of normal breast tissue or simple mastectomy (removal of the entire breast, but without removing the axillary lymph nodes).

WHAT TREATMENTS ARE USED FOR NON-INVASIVE BREAST CANCER?

The management of non-invasive breast cancer, ductal carcinoma in situ and lobular carcinoma in situ, is much different than with invasive cancer of the breast. Treatment options are less clear cut in non- invasive cancer of the breast.

Ductal carcinoma in situ is a pre-invasive cancer. Its treatment is based on the risk of this disease evolving into an invasive cancer which is then life- threatening. Treatment options for ductal carcinoma in situ include lumpectomy, lumpectomy combined with radiation therapy, and simple mastectomy. A simple mastectomy is an operation which removes the entire breast, but does not remove the axillary lymph nodes as is done in a modified radical mastectomy.

If the area involved with ductal carcinoma is quite small (one centimeter or less) then simply removing this area alone may suffice. If the area of breast involved is larger, then further therapy is usually indicated, because the risk of the breast cancer recurring is reasonably high over the ensuing years. When the cancer recurs, 50% of the time the cancer is invasive. If a simple mastectomy is used to treat carcinoma in situ, the cure rate is 98-99%. Since all the remaining breast tissue is removed, there is no further breast tissue that remains in which a breast cancer can form. Why isn’t the cure rate 100%? This is due to the fact that a microscopic analysis of the cancer can miss a small area of invasive cancer. Therefore, there is a chance that the cancer can metastasize. Secondly, even with the best surgical technique, some breast tissue may remain after a mastectomy.

If a woman wishes to pursue breast conservation therapy and not mastectomy, then lumpectomy and radiation therapy to the remaining breast tissue is used. Data does not yet exist which confirms that this form of therapy is as effective as a simple mastectomy. The results of clinical trials which compare these two forms of therapy should be available within the next several years. Most doctors expect lumpectomy and radiation to compare quite favorably to mastectomy as it does with invasive cancer. There are some forms of ductal carcinoma in situ that are resistant to radiation therapy. The treatment for carcinoma in situ must be individualized in each woman’s case and she should be made aware of the relative risks and benefits of each treatment modality.

Lobular carcinoma in situ is not a pre-invasive cancer as is ductal carcinoma in situ. Rather, it represents a high risk potential for the development of invasive breast cancer. This risk is estimated to be approximately one percent per year. This risk is for both breasts because 50% of the time the invasive cancer will occur in the opposite breast in which the lobular carcinoma in situ was found. Additionally, lobular carcinoma in situ is multifocal (it occurs in many places or throughout the breast).

Since the risk of developing an invasive cancer is acceptably low to most women and their doctors, the usual recommendation is to perform yearly mammograms and to have a breast examination every six months for life. If a more aggressive approach is taken, the only logical choice that exists at this time is the removal of both breasts (bilateral simple mastectomy). This approach is sometimes justified in a woman with a strong family history of breast cancer, and/or the woman who is young at the time of the diagnosis. This is because the cumulative 1% per year risk of developing invasive cancer can be substantial after many years.

Lumpectomy with or without radiation does not significantly decrease the risk of developing an invasive breast cancer with lobular carcinoma in situ. A single mastectomy does not seem to be the answer either, since the invasive cancer can occur in either breast. This is yet another area of breast disease that requires more research and knowledge to optimize management and offer treatment options.

CAN WOMEN HELP THEMSELVES ADDRESS BREAST CANCER ISSUES?

As can be seen, the management of breast cancer is quite varied and complex. The subtleties of each case make it most important for each woman to discuss her options with the health professionals involved in her care.

The best chance of eliminating breast cancer is prevention. However, we currently do not have the knowledge to prevent breast cancer. The capability of diagnosing breast cancer in a much earlier stage than in previous years does exist. Early diagnosis of breast cancer can be achieved with routine mammography and early biopsy of suspicious lesions. The earlier a breast cancer is found, the better the chances of a cure.

Current American Cancer Society guidelines for mammography recommend that a woman should have a baseline mammogram between the ages of 35 and 40. She should have a mammogram every other year between the ages of 40 and 50. Beyond the age of 50, a woman should have a yearly mammogram.

The more the community is educated about breast cancer issues, the greater the likelihood of controlling this deadly disease.

BREAST CANCER AT A GLANCE

* One in every eight women in the United States develops breast cancer.
* The causes of breast cancer are not yet fully known although a number of risk factors have been identified.
* Breast cancer is diagnosed with self- and physician- examination of the breasts, mammography, ultrasound testing, and biopsy.
* There are many types of breast cancer that differ in their capability of spreading (metastasize) to other body tissues.
* Treatment of breast cancer depends on the type and location of the breast cancer, as well as the age and health of the patient.
* The American Cancer Society recommends that a woman should have a baseline mammogram between the ages of 35 and 40 years. Between 40 and 50 years of age mammograms are recommended every other year. After age 50 years, yearly mammograms are recommended.

Breast Cancer Case Studies: –

Treatment of left-sided breast cancer using Active Breathing Coordinator™ at William Beaumont Hospital, USA

Image guided IMRT of a left-sided breast cancer in the case of a patient with pectus excavatum using Elekta Synergy® at Universitätsklinikum Mannheim, Germany